DESCRIPTION (adapted from applicants abstract): The long-range goal of the proposed research is to improve understanding of the neural mechanisms of gynecological pain. The studies use behavioral and electrophysiological methods to characterize escape behaviors and CNS activity elicited by pelvic organ stimulation in female rats under various normal and pathological conditions. Specific aims for the next 5 years focus on mechanisms of vaginal hyperalgesia (VAGH) and will test three hypotheses. (1) Reproductive senescence and VAGH: Vaginal sensitivity in women increases after menopause to produce VAGH. This VAGH is thought to be due to the effects of estrogen loss on vaginal tissue. The hypothesis that senescence-VAGH is associated with hypoestrogenic-conditions and changes in physical properties of the vagina will be tested in rats by using behavioral methods in awake rats to study how escape responses to vaginal distension and how vaginal tone both changes as the rats age through senescence and following hormonal manipulations. (2) Endometriosis and VAGH: Viable endometrial tissue outside the uterus in women is associated with infertility and pelvic pain, including VAGH. Because estrogen is necessary for ectopic endometrial viability, behavioral methods and hormonal manipulations will be used on a rat model of endometriosis to test the hypothesis that endometriosis-VAGH, in contrast to senescence-VAGH, depends upon estrogen and is independent of vaginal tone. (3) CNS mechanisms: Despite the fact that sensory afferents of the rat female reproductive tract convey highly specific and topographically-organized information to the CNS, many neurons in the spinal cord and thalamus respond convergently to stimulation of pelvic organs and skin, and the responses can change depending on changing CNS control factors. Even more surprisingly, this situation appears also to apply to neurons in the two other ports-of-entry for pelvic information to the CNS, the gracile and solitary nuclei, suggesting that these two portal nuclei warrant inclusion, along with the spinal cord, in studies of CNS pain mechanisms. Accordingly, electrophysiological studies will compare how responses to stimulation of pelvic organs and skin by neurons in the gracile and solitary nuclei, as well as in the spinal cord, change as a consequence of estrous state, senescence-VAGH, and endometrious-VAGH.